Inhibition of Granulocyte-Macrophage Colony Formation In Vitro by Substituted Isatin Thiosemicarbazones

Abstract

The 1-methylisatin derivative of isatin thiosemicarbazone was previously shown to inhibit granulocyte-macrophage colony growth in vitro by an action at the early stages of colony development. The parent compound isatin thiosemicarbazone and 25 other derivatives were tested, and a wide range of activity was found (50% colony inhibition from 0.07 to > 100 ,ug per ml of culture). High activity was not associated with any specific substituent, although 1-methyl or 1-ethyl isatin groups in association with 4'4' morpholino or 4'4' tetramethylene thiosemicarbazone substitutions were within the most active group. No correlation between the antimarrow and known antiviral activities of these compounds was apparent. Two of the more active compounds were compared with methisazone and were shown to have the same property of selective action on the early stages of granulocyte-macrophage differentiation in culture. It is suggested that this group of compounds might possibly provide some useful antileukemia agents.

Unraveling the binding interaction and kinetics of a prospective anti-HIV drug with a model transport protein: results and challenges

“…10,11 In fact, some derivatives of isatins (e.g., 5-fluoro-3-substituted-2-oxoindole) have already been implemented in the treatment of gastrointestinal stromal tumors, 12 and advanced renal cell carcinoma, 13 while many other halogenated derivatives are in use for treatment of cancer and leukemia. 14 Apart from these, isatin derivatives have also claimed their proficiency as drugs for arteriospasm, hypertension, migraines, coronary, ischemic heart diseases, cardiac arrhythmia and other disorders. 15,16 Probably, the most demanding thrust of research activities surrounding the isatin derivatives has emanated from their antifungal 17 and antiviral 18,19 properties.…”

The Thiosemicarbazones

“…The initial quantitative studies on the ability of thiosemicarbazones to inhibit the immune response in mice were carried out by McNEILL (1972McNEILL ( , 1973 and McNEILL et al (1972). The humoral response to sheep red blood cells (see Sect.…”

“…He felt that this indicated a selective mode of action of the drug, although there was no change in the relative frequency of granulocyte and macrophage colonies. McNEILL (1973) extended these studies on colony inhibition, using 25 derivatives of IBT (see Sect. G.IV).…”

Synthesis ofN-Arylisatins by the Reaction of Arynes with Methyl 2-Oxo-2-(arylamino)acetates

“…Isatins are highly sought after compounds because of their biological and medicinal activities . They exhibit a broad array of biologically important properties, including antifungal, antiviral, anti-HIV, anti-AIDS, antiprotozoal, anticancer, antitumor, and antileukemia properties …”